Low T could hasten time to post-RP biochemical recurrence.

[pjoshea13]

New study below.

Off-topic for this group, but I like to report studies that erode the assumption that testosterone is "fuel" for PCa.

"Men with low levels of free testosterone 3 months after undergoing radical prostatectomy could face increased chance of early recurrence of prostate cancer, according to researchers from the University of California Irvine."

"It’s a finding that could point to the benefit of testosterone replacement therapy in men with low free testosterone and total testosterone.

"“We didn’t expect free testosterone to be an independent predictor of recurrence,” co-author Linda M. Huynh, MS, clinical research coordinator and assistant specialist in the department of urology at University of California Irvine, told Urology Times during the AUA annual meeting in Chicago.

"The study confirms that higher levels of free testosterone do not further the progression of prostate cancer, the authors say. Meanwhile, low levels of free testosterone may hasten time to biochemical recurrence following radical prostatectomy.

"The relationship between testosterone and prostate cancer has long been a source of controversy. For years, researchers believed testosterone replacement therapy increased men’s chances of developing prostate cancer. Now, some new studies are exploring whether testosterone replacement therapy could reduce the risk of aggressive prostate cancer. A study presented at the European Association of Urology annual congress in Barcelona found a 53% reduction in recurrence of prostate cancer among patients treated with testosterone therapy following robot-assisted radical prostatectomy.

"Meanwhile, literature supports the protective role that high levels of free testosterone play in preventing cardiovascular disease, diabetes mellitus, and other types of metabolic disorders, the University of California Irvine researchers say. They also point to recent data that show low levels of testosterone could be an independent risk factor for high-grade prostate cancer.

"The authors sought to examine the relationship between free testosterone and biochemical recurrence in radical prostatectomy patients.

"Under the direction of senior author Thomas Ahlering, MD, the group studied 800 patients who underwent robot-assisted radical prostatectomy from December 2009 through June 2018 for primary treatment of localized prostate cancer. Each patient was treated by a single surgeon, and cases from four surgeons were analyzed.

"The authors measured patients’ total testosterone and free testosterone levels prior to surgery as well as 3 months after surgery. They also measured PSA levels, the pathologic stage of the cancer, and the pathologic grade. Only patients for whom each of these values was available were included for analysis.

"The primary and secondary outcomes ­measured were biochemical recurrence (defined as two consecutive PSA values of 0.2 ng/dL or greater) and time to biochemical recurrence, respectively. Median follow-up time was 3.2 years following radical prostatectomy.

"About one in five patients (20.8%) experienced biochemical recurrence. Among these patients, preoperative free testosterone as well as free testosterone levels after 3 months were significantly lower than those of other patients in the study.

"After adjusting for age, lower levels of free testosterone 3 months after radical prostatectomy independently predicted time to biochemical recurrence as well as the pathologic stage of the cancer."

-Patrick

urologytimes.com/mens-healt...

urologytimes.com/mens-healt...

[Shooter1]

Guess that leaves me out with PSA of 64 6 weeks after prostatectomy . 54 before surgery. 6.4 at 3 mo PSA check and on Lupron.

[kaptank]

Pretty clear and not at all off topic. The myth that testosterone "fuels cancer" needs to be busted for all our good. The evidence has been in for well over a decade that the myth has no merit at all. What we still don't know is the exact relationship of T with PCa and we need to find out for management and treatment options. The "saturation model" is a first rough working guess. Its clearly more complex.

[middlejoel in reply to kaptank]

So if testosterone does not fuel prostate cancer, what is the rational for being on ADT?

[Longterm101 in reply to middlejoel]

Support big Pharma !!

[Tommyj2 in reply to middlejoel]

More specifically.... If T does not fuel Prostate Cancer why does lowering it reduce PSA ( or is it being posited that lowering PSA is an artifact and is not really addressing the Pca??) What then IS the mechanism of ADT? It appears clear that it has beneficial results.

[pjoshea13 in reply to Tommyj2]

Tommy,

ADT (T ablation) does not target PCa progenitor cells (so-called stem cells). They do not need T. The cancer never goes away when ADT is monotherapy or coupled with an androgen receptor antagonist.

As to PSA, the test was envisioned as a useful way of detecting treatment failure - not as a screening tool. In a screened population, PSA may rise for reasons other than PCa. But in PCa treated with curative intent, changes in PSA are always due to death/proliferation of PSA-producing cancer cells. It can't shed light on cells that do not produce PSA.

-Patrick

[Tommyj2 in reply to pjoshea13]

IS there a treatment out there that directs itself to the progenitor cells?? For a brief while I thought that I was beginning to get a handle on the process of PCA and the treatment involved but ever since joining this forum I am more unsure than ever..... I just had a precipitous jump in my PSA after a doubling time of 1.73yrs for the past several years and about to embark on ADT....disquieting to read posts that call into question the efficacy of standard of care Tx.....

[pjoshea13 in reply to Tommyj2]

Tommy,

From my limited reading, I formed the view that treatments tend to force cells into a stem-like state. Or rather, select for cells that demonstrate stem-like properties. So my view has been that one needs to be careful with the timing of aggressive therapies.

(I had lunch with Nalakrats on Thursday & he has a different view.)

There is some hope:

"Chemopreventive Effect of PSP Through Targeting of Prostate Cancer Stem Cell-Like Population" [1]

"Metformin as an anti-cancer agent: actions and mechanisms targeting cancer stem cells." [2]

-Patrick

[1] journals.plos.org/plosone/a...

[2] ncbi.nlm.nih.gov/pubmed/293...

[pjoshea13 in reply to middlejoel]

Joel,

Prostatic cell division requires the invovement of the androgen receptor [AR] axis. Testosterone [T] is an essential part of that, but you can double your T level & it will have no effect on the rate of cell division.

Note that an AR antagonist as monotherapy will halt PCa growth, but castration 'therapy' has been standard for ~75 years.

If T drives PCa, how come ADT fails for most in 18-24 months? Castration would be a cure if T was indeed the "driver".

-Patrick

[middlejoel in reply to pjoshea13]

Patrick,

This is way over my head and pay scale but for me. ever since 2006, its been T converted to DHT drives PCa. So the treatment is to reduce production of testosterone by getting to castrate level using an LHRH agonist such as Lupron or to block the AR receptor by using an antagonist such as Casodex. My understanding is that second line treatment with Zytiga and Xtandi follow the same theory. Yeah, sure eventually the drugs stop work but it seems to me that the conventional treatment for those that are recently affected is still ADT. What am I missing here?

[pjoshea13 in reply to middlejoel]

Joel,

Yes, conventional treatment is still ADT, or rather, targets the AR axis.

Back when I was born, ADT was a miracle treatment. The actuarial tables for American males at that time show dismal survival figures for the general population. So, if ADT gave a man 5 years, it was a big deal.

The tables today are quite different. The life expectancy for a man age 70 is almost 15 years. And for a man age 55, normal life expectancy is 25 years. AR axis therapies do not deliver what the PCa population needs.

Androgen ablation is palliative - never curative. T is growth-permissive, not growth-promoting. The common view that T is fuel for PCa is false.

-Patrick

[Jbooml]

For me it’s more about free ctc’s than T.....stop the flood of circulating cancer cells and you stop the cancer.